Journal
CELLS
Volume 11, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/cells11071242
Keywords
N-glycosylation; neural cell adhesion molecule; membrane targeting; mutagenesis; ER
Categories
Funding
- National Research Foundation of Korea [NRF-2020R1A2C201128811, NRF-2020R1A5A8017671]
- Korean government (MSIT)
Ask authors/readers for more resources
Neuronal growth regulator 1 (NEGR1) is involved in neural cell communication and synapse formation, and its N-glycan residues play important roles in the folding, trafficking, and homodimer formation of NEGR1 protein.
Neuronal growth regulator 1 (NEGR1) is a brain-enriched membrane protein that is involved in neural cell communication and synapse formation. Accumulating evidence indicates that NEGR1 is a generic risk factor for various psychiatric diseases including autism and depression. Endoglycosidase digestion of single NEGR1 mutants revealed that the wild type NEGR1 has six putative N-glycosylation sites partly organized in a Golgi-dependent manner. To understand the role of each putative N-glycan residue, we generated a series of multi-site mutants (2MT-6MT) with additive mutations. Cell surface staining and biotinylation revealed that NEGR1 mutants 1MT to 4MT were localized on the cell surface at different levels, whereas 5MT and 6MT were retained in the endoplasmic reticulum to form highly stable multimer complexes. This indicated 5MT and 6MT are less likely to fold correctly. Furthermore, the removal of two N-terminal sites N75 and N155 was sufficient to completely abrogate membrane targeting. An in vivo binding assay using the soluble NEGR1 protein demonstrated that glycans N286, N294 and N307 on the C-terminal immunoglobulin-like domain play important roles in homophilic interactions. Taken together, these results suggest that the N-glycan moieties of NEGR1 are closely involved in the folding, trafficking, and homodimer formation of NEGR1 protein in a site-specific manner.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available